EP0245952A2 - Buccal tablet comprising etorphine or a salt thereof - Google Patents
Buccal tablet comprising etorphine or a salt thereof Download PDFInfo
- Publication number
- EP0245952A2 EP0245952A2 EP87303121A EP87303121A EP0245952A2 EP 0245952 A2 EP0245952 A2 EP 0245952A2 EP 87303121 A EP87303121 A EP 87303121A EP 87303121 A EP87303121 A EP 87303121A EP 0245952 A2 EP0245952 A2 EP 0245952A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- etorphine
- tablet
- weight
- locust bean
- mixture
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
Definitions
- This invention relates to pharmaceutical compositions and in particular to compositions containing etorphine.
- Etorphine (INN for 7, ⁇ -1-(S)-hydroxy-1-methylbutyl-6, 14- endo etheno-6,7,8,14-tetrahydro-oripavine) in the form of the free base or its salts is a potent analgesic in both animals and man.
- analgesia Upon intramuscular administration to patients with a difficult pain control problem analgesia has been observed within 2-3 minutes of injection and has persisted for 1.5-2 hours. The majority of these patients were given etorphine in the dose range 50-400 ⁇ g which was judged to provide greater benefit relative to other analgesics.
- Studies in dog have shown etorphine to be more effective than morphine after sublingual administration. In patients sublingual etorphine was found to be beneficial with onset of effect occurring less than 10 minutes after tablet dissolution with the analgesic effect lasting for 1.5 to 4 hours.
- a buccal tablet comprising etorphine or a salt therof, at least one monosaccharide, disaccharide or a mixture thereof, and a mixture of xanthan gum and locust bean gum in a weight ratio of 3:1 to 1:1, wherein the total weight of the mono-and/or di-saccharides relative to the combined weight of the xanthan and locust bean gums is in the ratio of 20:1 to 3:1 and preferably in the ratio of 12:1 to 5:1.
- Suitable monosaccharides include glucose, galactose, fructose, mannose, mannitol and sorbitol.
- the disaccharides include maltose, lactose and sucrose, a preferred carrier being sucrose.
- the tablets will normally contain 50 to 200 ⁇ g etorphine hydrochloride and conveniently 100 ⁇ g.
- the locust bean gum is preferably a cold-water dispersible type such as Meyprodyn 200 (Registered Trade Mark, Meyhall Chemical A.G. Switzerland).
- the tablets will preferably contain binding agents such as polyvinylpyrrolidone, lubricating agents such as magnesium stearate and/or glidants such as talc.
- binding agents such as polyvinylpyrrolidone, lubricating agents such as magnesium stearate and/or glidants such as talc.
- the tablets are prepared by standard tabletting procedures in which various components are blended together and the mixture directly compressed or else there is a pregranulation stage using for example a wet granulation with aqueous ethanol or isopropanol followed by the tabletting.
- the buccal tablets of the present invention are placed between the gingival surface of the jaw and the buccal mucosa where they gel by water absorption to produce a soft hydrated tablet which may be retained in position giving prolonged and controlled release of the drug by diffusion for up to two hours.
- Buccal tablets (60 mg) were prepared having the following compositions: where x and y are respectively:
- the tablets were prepared by blending together the xanthan gum, locust bean gum, polyvinylpyrrolidone, and sucrose. The mixed powders were then wet granulated using an 8:5 (v/v) ethanol:water mixture, containing the dissolved etorphine HCl, by hand using a mortar and pestle. The damp granules were dried at 45°C. After drying the mass was passed through a 500 ⁇ m sieve, blended with the talc and magnesium stearate and compressed into 5.56 mm diameter normal concave tablets of nominal weight 60 mg and breaking strength 2-5 kp using a single punch tablet press.
- Buccal tablets (60 mg) were prepared, having the composition of Examples 1-3, but also including the colouring agent erythrosine (6 ⁇ g) added to the 8:5 ethanol:water granulating fluid.
- Buccal tablets (80 mg) were prepared having the composition: where x and y are respectively:
- the granules bulk mixes were prepared as in Examples 1 3 and the tablets of nominal weight 80 mg and 6.35 mm normal concave profile were compressed on a single punch tablet press.
- Buccal tablets (80 mg) were prepared, having the composition of Examples 7-9, but also including the colouring agent erythrosine (20 ⁇ g) added to the 8:5 ethanol:water granulating fluid.
- Buccal tablets (80 mg) similar to those of Examples 7-9 were prepared using lactose B.P. in the place of the sucrose.
- Buccal tablets (80 mg) similar to those of Examples 7-9 were prepared using mannitol in the place of the sucrose.
- Buccal tablets (80 mg) similar to those of Examples 7-9 were prepared using anhydrous dextrose B.P. in the place of the sucrose.
- Buccal tablets (80 mg) similar to those of Examples 7-9 were prepared using fructose in the place of the sucrose.
- Buccal tablets (80 mg) similar to those of Examples 7-9 were prepared using sorbitol in the place of the sucrose.
- the in-vitro release rate of the buccal tablets was investigated using a method based on British Pharmacopoeia 1980, Volume II, A114. Tablets were placed in a standard wire gauze basket (Copley Instruments (Nottingham) Limited) and rotated at 100 rpm in 100 ml of 0.1M phosphate buffer (pH 6.7) contained in a 150 ml tall form beaker, placed in a water bath maintained at 37 ⁇ 1°C. At intervals 200 ⁇ l aliquots were removed and replaced by 200 ⁇ l buffer.
- sample solutions 50 ⁇ l were assayed for etorphine content by high performance liquid chromatography using 1% aqueous ammonium acetate:methanol (40:60) as the mobile phase delivered at 2 ml/min (by a Kontron 420 pump) through a 10 cm ⁇ 0.46 cm id stainless steel column packed with Hypersil 5 ⁇ m ODS packing material.
- Etorphine content was monitored by electrochemical detection using a BAS LC4-B detector at a potential of +0.75 volts (0.5nA f.s.d.). Quantitation was carried out automatically using a Hewlett-Packard 3390 or 3393 computing integrator.
- the Table presents data of in-vitro dissolution of Examples 1 and 2.
- Tables containing xanthan/Meyprodyn gum mixtures gel in the mouth by water absorption to give a soft tablet which adheres to the buccal mucosa and subsequently remains in position for up to two hours.
- Comparative tablets containing none of the gum mixture do not gel, but tend to remain in position as the tablet wets, however when fully hydrated the tablet disintegrates to hard coarse particles that have no adhesive properties.
- Such tablets have undesirable organoleptic properties and their inherent inability to adhere to the mucosa makes them less likely to give satisfactory buccal absorption and makes them less acceptable than the soft buccal tablets of this invention.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Emergency Medicine (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
- This invention relates to pharmaceutical compositions and in particular to compositions containing etorphine.
- Etorphine (INN for 7,α-1-(S)-hydroxy-1-methylbutyl-6, 14-endoetheno-6,7,8,14-tetrahydro-oripavine) in the form of the free base or its salts is a potent analgesic in both animals and man. Upon intramuscular administration to patients with a difficult pain control problem analgesia has been observed within 2-3 minutes of injection and has persisted for 1.5-2 hours. The majority of these patients were given etorphine in the dose range 50-400 µg which was judged to provide greater benefit relative to other analgesics. Studies in dog have shown etorphine to be more effective than morphine after sublingual administration. In patients sublingual etorphine was found to be beneficial with onset of effect occurring less than 10 minutes after tablet dissolution with the analgesic effect lasting for 1.5 to 4 hours.
- Experiments in animals have shown that etorphine passes rapidly across the buccal mucosa and into the systemic circulation. We have now developed a buccal tablet that controls the release of the drug and thereby slows down the rate of absorption into the buccal tissue and thus increases the duration of analgesia.
- According to this invention there is provided a buccal tablet comprising etorphine or a salt therof, at least one monosaccharide, disaccharide or a mixture thereof, and a mixture of xanthan gum and locust bean gum in a weight ratio of 3:1 to 1:1, wherein the total weight of the mono-and/or di-saccharides relative to the combined weight of the xanthan and locust bean gums is in the ratio of 20:1 to 3:1 and preferably in the ratio of 12:1 to 5:1.
- Suitable monosaccharides include glucose, galactose, fructose, mannose, mannitol and sorbitol. The disaccharides include maltose, lactose and sucrose, a preferred carrier being sucrose.
- The tablets will normally contain 50 to 200 µg etorphine hydrochloride and conveniently 100 µg.
- The locust bean gum is preferably a cold-water dispersible type such as Meyprodyn 200 (Registered Trade Mark, Meyhall Chemical A.G. Switzerland).
- The tablets will preferably contain binding agents such as polyvinylpyrrolidone, lubricating agents such as magnesium stearate and/or glidants such as talc.
- The tablets are prepared by standard tabletting procedures in which various components are blended together and the mixture directly compressed or else there is a pregranulation stage using for example a wet granulation with aqueous ethanol or isopropanol followed by the tabletting.
- The buccal tablets of the present invention are placed between the gingival surface of the jaw and the buccal mucosa where they gel by water absorption to produce a soft hydrated tablet which may be retained in position giving prolonged and controlled release of the drug by diffusion for up to two hours.
- The invention is illustrated by the following Examples:
-
- The tablets were prepared by blending together the xanthan gum, locust bean gum, polyvinylpyrrolidone, and sucrose. The mixed powders were then wet granulated using an 8:5 (v/v) ethanol:water mixture, containing the dissolved etorphine HCl, by hand using a mortar and pestle. The damp granules were dried at 45°C. After drying the mass was passed through a 500 µm sieve, blended with the talc and magnesium stearate and compressed into 5.56 mm diameter normal concave tablets of nominal weight 60 mg and breaking strength 2-5 kp using a single punch tablet press.
- Buccal tablets (60 mg) were prepared, having the composition of Examples 1-3, but also including the colouring agent erythrosine (6 µg) added to the 8:5 ethanol:water granulating fluid.
-
- The granules bulk mixes were prepared as in Examples 1 3 and the tablets of nominal weight 80 mg and 6.35 mm normal concave profile were compressed on a single punch tablet press.
- Buccal tablets (80 mg) were prepared, having the composition of Examples 7-9, but also including the colouring agent erythrosine (20 µg) added to the 8:5 ethanol:water granulating fluid.
- Buccal tablets (80 mg) similar to those of Examples 7-9 were prepared using lactose B.P. in the place of the sucrose.
- Buccal tablets (80 mg) similar to those of Examples 7-9 were prepared using mannitol in the place of the sucrose.
- Buccal tablets (80 mg) similar to those of Examples 7-9 were prepared using anhydrous dextrose B.P. in the place of the sucrose.
- Buccal tablets (80 mg) similar to those of Examples 7-9 were prepared using fructose in the place of the sucrose.
- Buccal tablets (80 mg) similar to those of Examples 7-9 were prepared using sorbitol in the place of the sucrose.
- The in-vitro release rate of the buccal tablets was investigated using a method based on British Pharmacopoeia 1980, Volume II, A114. Tablets were placed in a standard wire gauze basket (Copley Instruments (Nottingham) Limited) and rotated at 100 rpm in 100 ml of 0.1M phosphate buffer (pH 6.7) contained in a 150 ml tall form beaker, placed in a water bath maintained at 37±1°C. At intervals 200 µl aliquots were removed and replaced by 200 µl buffer. The sample solutions (50 µl) were assayed for etorphine content by high performance liquid chromatography using 1% aqueous ammonium acetate:methanol (40:60) as the mobile phase delivered at 2 ml/min (by a Kontron 420 pump) through a 10 cm × 0.46 cm id stainless steel column packed with Hypersil 5 µm ODS packing material. Etorphine content was monitored by electrochemical detection using a BAS LC4-B detector at a potential of +0.75 volts (0.5nA f.s.d.). Quantitation was carried out automatically using a Hewlett-Packard 3390 or 3393 computing integrator.
-
- From the results it can be seen that the rate of drug release decreases with increasing xanthan and locust bean gum content.
- Tables containing xanthan/Meyprodyn gum mixtures gel in the mouth by water absorption to give a soft tablet which adheres to the buccal mucosa and subsequently remains in position for up to two hours.
- Comparative tablets containing none of the gum mixture do not gel, but tend to remain in position as the tablet wets, however when fully hydrated the tablet disintegrates to hard coarse particles that have no adhesive properties. Such tablets have undesirable organoleptic properties and their inherent inability to adhere to the mucosa makes them less likely to give satisfactory buccal absorption and makes them less acceptable than the soft buccal tablets of this invention.
Claims (6)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB8608818 | 1986-04-11 | ||
GB868608818A GB8608818D0 (en) | 1986-04-11 | 1986-04-11 | Pharmaceutical compositions |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0245952A2 true EP0245952A2 (en) | 1987-11-19 |
EP0245952A3 EP0245952A3 (en) | 1988-02-10 |
Family
ID=10596029
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP87303121A Withdrawn EP0245952A3 (en) | 1986-04-11 | 1987-04-09 | Buccal tablet comprising etorphine or a salt thereof |
Country Status (7)
Country | Link |
---|---|
US (1) | US4829056A (en) |
EP (1) | EP0245952A3 (en) |
AU (1) | AU7141087A (en) |
DK (1) | DK184087A (en) |
GB (2) | GB8608818D0 (en) |
PT (1) | PT84662B (en) |
ZA (1) | ZA872520B (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0376891A1 (en) * | 1988-12-30 | 1990-07-04 | Ciba-Geigy Ag | Coated adhesive tablets |
EP0581676A2 (en) * | 1992-07-30 | 1994-02-02 | Edward Mendell Co., Inc. | Agglomerated hydrophilic complexes with multi-phasic release characteristics |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4994276A (en) * | 1988-09-19 | 1991-02-19 | Edward Mendell Co., Inc. | Directly compressible sustained release excipient |
US5128143A (en) * | 1988-09-19 | 1992-07-07 | Edward Mendell Co., Inc. | Sustained release excipient and tablet formulation |
US5169639A (en) * | 1988-09-19 | 1992-12-08 | Edward Mendell Co., Inc. | Controlled release verapamil tablets |
US5135757A (en) * | 1988-09-19 | 1992-08-04 | Edward Mendell Co., Inc. | Compressible sustained release solid dosage forms |
US5073374A (en) * | 1988-11-30 | 1991-12-17 | Schering Corporation | Fast dissolving buccal tablet |
US5112616A (en) * | 1988-11-30 | 1992-05-12 | Schering Corporation | Fast dissolving buccal tablet |
FR2649611A1 (en) * | 1989-07-13 | 1991-01-18 | Philippe Perovitch | Process for preparing a dosage form of a therapeutic composition, in particular one based on aspirin |
US5683721A (en) * | 1990-07-26 | 1997-11-04 | Perovitch; Philippe | Galenic preparation of therapeutic composition comprising aspirin |
JPH08504189A (en) * | 1992-09-21 | 1996-05-07 | キン、ボーイ | Identification and use of low / non-epileptic opioid analgesics |
US5633259A (en) * | 1992-09-21 | 1997-05-27 | United Biomedical, Inc. | Method for identification of low/non-addictive opioid analgesics and the use of said analgesics for treatment of opioid addiction |
US5330761A (en) * | 1993-01-29 | 1994-07-19 | Edward Mendell Co. Inc. | Bioadhesive tablet for non-systemic use products |
US5656284A (en) * | 1995-04-24 | 1997-08-12 | Balkin; Michael S. | Oral transmucosal delivery tablet and method of making it |
WO1997026865A1 (en) * | 1996-01-29 | 1997-07-31 | Edward Mendell Co., Inc. | Sustained release excipient |
MX9801835A (en) * | 1996-07-08 | 1998-08-30 | Mendell Co Inc Edward | Sustained release matrix for high-dose insoluble drugs. |
US6197331B1 (en) | 1997-07-24 | 2001-03-06 | Perio Products Ltd. | Pharmaceutical oral patch for controlled release of pharmaceutical agents in the oral cavity |
IN186245B (en) | 1997-09-19 | 2001-07-14 | Ranbaxy Lab Ltd | |
US6319510B1 (en) | 1999-04-20 | 2001-11-20 | Alayne Yates | Gum pad for delivery of medication to mucosal tissues |
US7282217B1 (en) | 2003-08-29 | 2007-10-16 | Kv Pharmaceutical Company | Rapidly disintegrable tablets |
GB0320854D0 (en) | 2003-09-05 | 2003-10-08 | Arrow No 7 Ltd | Buccal drug delivery |
FR2972327B1 (en) * | 2011-03-11 | 2017-08-11 | Laboratoires Le Stum | MUCOADHESIVE NUTRACEUTICAL COMPOSITION COMPRISING ANTIOXIDANT ASSOCIATION |
US10758329B1 (en) | 2019-08-20 | 2020-09-01 | Raymond L. Wright, III | Hydrating mouth guard |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR893228A (en) * | 1941-07-03 | 1944-06-02 | Ste Ind Chim Bale | Method of manufacturing vehicles which can be used with active substances |
GB981372A (en) * | 1960-05-04 | 1965-01-27 | Pfizer Ltd | Pharmaceutical formulations for oral administration to animals |
DE2758942A1 (en) * | 1975-07-18 | 1979-07-05 | Abbott Lab | CHEWABLE TABLETS WITH ERYTHROMYCIN |
EP0095944A2 (en) * | 1982-06-02 | 1983-12-07 | Takeda Chemical Industries, Ltd. | Anti-androgenic preparation for oral cavity administration |
EP0107941A1 (en) * | 1982-10-07 | 1984-05-09 | Takeda Chemical Industries, Ltd. | Soft buccal |
EP0144243A1 (en) * | 1983-12-06 | 1985-06-12 | Reckitt And Colman Products Limited | Analgesic compositions |
EP0205282A2 (en) * | 1985-06-11 | 1986-12-17 | Euroceltique S.A. | Oral pharmaceutical composition |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2407486A (en) * | 1941-11-21 | 1946-09-10 | Du Pont | Veterinary compositions |
US3218232A (en) * | 1962-11-09 | 1965-11-16 | American Home Prod | Method for relieving depression and composition therefor |
US3557016A (en) * | 1965-10-22 | 1971-01-19 | Kelco Co | Heat reversible gel and method for preparing same |
US4038206A (en) * | 1976-01-15 | 1977-07-26 | General Mills Chemicals, Inc. | Hydroxyalkyl locust bean/xanthomonas hydrophilic colloid blends |
US4126684A (en) * | 1976-02-11 | 1978-11-21 | Ciba-Geigy Corporation | 4-amino-3-p-halophenylbutyric acids and their derivatives used in the control of narcotic abuse |
GB1604644A (en) * | 1977-07-22 | 1981-12-09 | Wellcome Found | Biologically active pentapeptide amides |
GB1604850A (en) * | 1977-11-24 | 1981-12-16 | Wellcome Found | Biologically active peptides |
US4315936A (en) * | 1979-12-17 | 1982-02-16 | Ortho Pharmaceutical Corporation | Analgesic composition |
US4598087A (en) * | 1983-12-06 | 1986-07-01 | Warner-Lambert Company | Substituted trans-1,2-diaminocyclohexyl amide compounds |
US4599342A (en) * | 1984-01-16 | 1986-07-08 | The Procter & Gamble Company | Pharmaceutical products providing enhanced analgesia |
GB8426152D0 (en) * | 1984-10-16 | 1984-11-21 | Reckitt & Colmann Prod Ltd | Medicinal compositions |
US4559326A (en) * | 1985-01-31 | 1985-12-17 | Pfizer Inc. | Antiinflammatory compositions and methods |
US4673679A (en) * | 1986-05-14 | 1987-06-16 | E. I. Du Pont De Nemours And Company | Use of prodrugs of 3-hydroxymorphinans to prevent bitter taste upon buccal, nasal or sublingual administration |
-
1986
- 1986-04-11 GB GB868608818A patent/GB8608818D0/en active Pending
-
1987
- 1987-04-08 ZA ZA872520A patent/ZA872520B/en unknown
- 1987-04-09 EP EP87303121A patent/EP0245952A3/en not_active Withdrawn
- 1987-04-10 DK DK184087A patent/DK184087A/en not_active Application Discontinuation
- 1987-04-10 AU AU71410/87A patent/AU7141087A/en not_active Abandoned
- 1987-04-10 PT PT84662A patent/PT84662B/en unknown
- 1987-04-10 US US07/037,191 patent/US4829056A/en not_active Expired - Fee Related
- 1987-04-10 GB GB8708587A patent/GB2188843B/en not_active Expired - Lifetime
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR893228A (en) * | 1941-07-03 | 1944-06-02 | Ste Ind Chim Bale | Method of manufacturing vehicles which can be used with active substances |
GB981372A (en) * | 1960-05-04 | 1965-01-27 | Pfizer Ltd | Pharmaceutical formulations for oral administration to animals |
DE2758942A1 (en) * | 1975-07-18 | 1979-07-05 | Abbott Lab | CHEWABLE TABLETS WITH ERYTHROMYCIN |
EP0095944A2 (en) * | 1982-06-02 | 1983-12-07 | Takeda Chemical Industries, Ltd. | Anti-androgenic preparation for oral cavity administration |
EP0107941A1 (en) * | 1982-10-07 | 1984-05-09 | Takeda Chemical Industries, Ltd. | Soft buccal |
EP0144243A1 (en) * | 1983-12-06 | 1985-06-12 | Reckitt And Colman Products Limited | Analgesic compositions |
EP0205282A2 (en) * | 1985-06-11 | 1986-12-17 | Euroceltique S.A. | Oral pharmaceutical composition |
Non-Patent Citations (1)
Title |
---|
CHEMICAL ABSTRACTS, vol. 68, 1968, page 165, abstract no. 1889n, Columbus, Ohio, US; G.F. BLANE: "Absence of respiratory depression in the newborn rat after maternal administration of etorphine by the sublingual route", & J. PHARM. PHARMACOL. 19(11), 781-2(1967) * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0376891A1 (en) * | 1988-12-30 | 1990-07-04 | Ciba-Geigy Ag | Coated adhesive tablets |
EP0581676A2 (en) * | 1992-07-30 | 1994-02-02 | Edward Mendell Co., Inc. | Agglomerated hydrophilic complexes with multi-phasic release characteristics |
EP0581676A3 (en) * | 1992-07-30 | 1995-06-07 | Mendell Co Inc Edward | Agglomerated hydrophilic complexes with multi-phasic release characteristics. |
EP1582205A2 (en) * | 1992-07-30 | 2005-10-05 | Penwest Phamaceuticals Co. | Agglomerated hydrophilic complexes with multi-phasic release characteristics |
EP1582205A3 (en) * | 1992-07-30 | 2008-07-30 | Penwest Pharmaceuticals Company | Agglomerated hydrophilic complexes with multi-phasic release characteristics |
Also Published As
Publication number | Publication date |
---|---|
DK184087D0 (en) | 1987-04-10 |
DK184087A (en) | 1987-10-12 |
PT84662B (en) | 1989-05-29 |
GB2188843A (en) | 1987-10-14 |
EP0245952A3 (en) | 1988-02-10 |
US4829056A (en) | 1989-05-09 |
GB2188843B (en) | 1990-04-11 |
GB8608818D0 (en) | 1986-05-14 |
ZA872520B (en) | 1987-11-25 |
GB8708587D0 (en) | 1987-05-13 |
AU7141087A (en) | 1987-10-15 |
PT84662A (en) | 1987-05-01 |
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